Welcome to the Immuneering Conference call to discuss the positive 12-month overall survival update from the company's ongoing Phase 2A trial of atebumetanib in first-line pancreatic cancer patients. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a Q&A session. To ensure that we have ample time to address everyone's questions, we would ask each person to limit themselves to one question and one follow-up. As a reminder, this call is being recorded today, Wednesday, January 7, 2026. I would now like to turn the conference over to Courtney Dugan, Vice President, Head of Investor Relations. Please go ahead.
Thank you, Operator. Joining us on the call today from Immuneering are Co-Founder and Chief Executive Officer Benjamin Zeskind, Chief Scientific Officer Brett Hall, Chief Medical Officer Igor Matushansky , Chief Accounting Officer and Treasurer Mallory Morales, and E.B. Braigwood, our Chief Business Officer. Please turn to Slide 2. During this call, management will make forward-looking statements, including statements related to its Phase 2A trial of atebumetanib, as well as the timing of additional data from the study and the company's development plans. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties. Factors that could cause these results to be different from these statements include factors the company describes in its securities filings, including its annual report on Form 10-K and quarterly reports on Form 10-Q.
Immuneering undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. With that, I will now turn the call over to Benjamin Zeskind, our Chief Executive Officer. Ben.
Thank you, Courtney. Good afternoon, everyone. We're excited to discuss our 12-month overall survival data for atebumetanib plus modified gemcitabine nab-paclitaxel in first-line pancreatic cancer patients. Please turn to Slide 3. This is a truly unique late-stage opportunity both in pancreatic cancer and beyond. Our deep cyclic inhibitors shrink tumors differently with exceptional durability and tolerability, and I think that's reflected in our clinical data to date and the clinical data we're sharing today. There are four key topics we'll cover on today's call. First, we will review the extraordinary overall survival data we continue to see in our ongoing Phase 2A study of atebumetanib plus chemotherapy in first-line pancreatic cancer. Next, you will hear about the dramatic improvements in quality of life we're seeing in certain patients treated with atebumetanib.
On our November earnings call, you heard about two such patients, and today you'll hear an equally compelling case study from Dr. Meredith Pelster at the Sarah Cannon Research Institute, describing a patient who experienced such a dramatic improvement in quality of life that she was able to regain meaningful independence in her day-to-day life, something that unfortunately is rare in this disease. We will then discuss our planned pivotal Phase 3 clinical trial, where dosing is expected to begin in the middle of this year in first-line pancreatic cancer patients. Lastly, we will review our broader pipeline and upcoming near-term milestones.
With a strong financial foundation from our financing in September and cash runway into 2029, we are well-funded to support multiple value-creating catalysts ahead, including the anticipated Phase 3 data readout, additional pancreatic cancer data, Phase 2 combination studies in lung cancer starting in 2026, as well as continued progress across our preclinical deep cyclic inhibitor platform. Please turn to Slide 4. Let's now dive into our 12-month data, starting with the most important endpoint: overall survival. What matters most to patients is how long they live, and overall survival remains the gold standard in oncology. We first shared impressive six-month overall survival data in June, and that was gratifying. It was even more exciting to report nine months' data in September, which continued to look extraordinary. Today, we are thrilled to report that this exceptional benefit continues at the 12-month mark and beyond.
At 12 months, overall survival is 64% in first-line pancreatic cancer patients treated with atebumetanib plus chemotherapy. That is an extraordinary result. Importantly, median overall survival still has not been reached. Please turn to Slide 5. When compared with historical benchmarks for standard of care gemcitabine plus nab-paclitaxel, or GNP, the separation is dramatic. In the pivotal MPACT study, 12-month overall survival for standard of care was approximately 35%. In our study, it is 64%, representing a 29-point absolute separation. Put another way, the probability of a patient being alive after 12 months in that landmark study was only about one-third, while in our trial, it is almost two-thirds. Moreover, median overall survival with standard of care was approximately 8.5 months, while our median has still not been reached, with a median follow-up time many months beyond that point at 13.4 months. Please turn to Slide 6.
This separation has been remarkably consistent over time. At six months, we observed a 27-point separation versus standard of care. At nine months, a 36-point separation, and now at 12 months, a 29-point separation. This consistency reflects the durability we designed atebumetanib to achieve, and it adds further robustness to the data. Importantly, overall survival remains 64% out to the median follow-up time of 13.4 months, which underscores the depth and durability of the benefit we're seeing, nearly double what would be expected with chemotherapy alone. Please turn to Slide 7. Now, while gemcitabine plus nab-paclitaxel is the most appropriate benchmark here, as it is the most commonly used global standard of care and the comparator in our upcoming Phase 3 trial, there are two other approved first-line regimens, FOLFIRINOX and NALIRIFOX combinations, which are generally reserved for younger, fitter patients due to their increased toxicity.
Yet, even when compared cross-trial against those regimens, atebumetanib continues to show a striking advantage. At 12 months, overall survival with FOLFIRINOX is approximately 48%, and with NALIRIFOX, it's approximately 45%, compared with 64% with atebumetanib plus chemotherapy in our study. Please turn to Slide 8. Turning to safety and tolerability, this has remained an important differentiator for atebumetanib. We designed this therapy to achieve both durability and tolerability, and the data continues to show very few harsh side effects. Only two categories of Grade 3 adverse events occurred in more than 10% of our patients: anemia and neutropenia. Both are well-known side effects of chemotherapy alone and, importantly, have not been observed with atebumetanib monotherapy. We are very pleased with the continued favorable safety and tolerability profile of atebumetanib, which we believe is a key differentiator in the competitive landscape. Please turn to Slide 9.
While overall survival is the primary endpoint in our Phase 3 study and the ultimate gold standard endpoint in oncology, the robustness of our data is further supported by strong separation from the pivotal MPACT study of standard of care GNP on secondary endpoints. We observed median progression-free survival of eight and a half months. The standard of care benchmark from MPACT was only five and a half months. We observed an overall response rate of 39%. The standard of care benchmark was 23%, and we observed a disease control rate of 81%. The standard of care benchmark was only 48%. Please turn to Slide 10. Baseline demographics also support the strength of these findings. Patients in our study were generally well-matched to those in prior pivotal trials with one notable difference: our population was meaningfully older.
In our trial, the median age was 69 compared to the low to mid-60s in historical studies. Moreover, more than two-thirds of our patients were over age 65. As such, demonstrating this degree of survival benefit in an older population further reinforces the significance of our results. Please turn to Slide 11. Now, we started with this original cohort of 34 first-line pancreatic cancer patients treated with atebumetanib plus modified gemcitabine nab-paclitaxel. And later, we decided to enroll an expanded cohort that includes these 34 patients and additional enrolled patients who are approaching sufficient median follow-up time. We plan to report overall survival in this expanded cohort of over 50 patients in the first half of this year. And I'm thrilled to say that the overall survival in the expanded cohort is trending consistently with overall survival in the original 34 patients. Please turn to Slide 12.
Now, behind these numbers are real patients experiencing meaningful benefit. On our November earnings call, Dr. Allyson Ocean at Weill Cornell and Dr. Gregory Botta at UC San Diego both spoke about how well their patients were doing on an atebumetanib combination, with Dr. Ocean describing a patient with a complete response who had, quote, "never felt better," and Dr. Botta describing a patient who was able to receive surgery with curative intent and had, "great quality of life." Today, we are honored to have Dr. Meredith Pelster from Sarah Cannon Research Institute join us on the call. Dr. Pelster will discuss a patient she is treating with atebumetanib plus gemcitabine nab-paclitaxel, a patient who is also experiencing dramatic improvements in quality of life, including regaining independence that had previously been lost.
This patient is part of the expanded cohort that we will be reporting on in the first half, and her experience is representative of what we are also seeing in many other patients treated with atebumetanib. So with that, let me hand the call over to Dr. Meredith Pelster.
Thank you, Ben. My name is Dr. Meredith Pelster, and I am a medical oncologist with a focus on treating patients with gastrointestinal cancers and serve as the associate director of gastrointestinal cancer research and executive chair of the Gastrointestinal Cancer Research Executive Committee for the Sarah Cannon Research Institute. I am also a Phase 1 investigator at the Sarah Cannon Research Institute Nashville Drug Development Unit and an investigator in Immuneering's Phase 2A study of atebumetanib. Over the years, I have treated many patients with pancreatic cancer and have seen firsthand the urgent need for new medicines. The case study I'm about to walk you through comes from the arm studying atebumetanib in combination with gemcitabine and nab-paclitaxel in first-line pancreatic cancer.
The patient is from the more recent group of patients after the company reopened the study for enrollment, so she is not one of the original 34 being reported today, but is part of the extended cohort of over 50 patients that the company plans to report on in the first half of this year. The patient is a 64-year-old female with metastatic pancreatic cancer with a KRAS G12V mutation who is being treated with daily atebumetanib plus modified gemcitabine nab-paclitaxel in the first line. The patient has now been on treatment for approximately five months and remains on treatment. The patient started with a substantial 8.8 centimeters of tumor burden across four target lesions: two located in the liver, one in the pancreas, and one in the peritoneum.
By the first scan, both of the liver mets had been rendered undetectable, and they have remained undetectable across two subsequent scans. The other two lesions have essentially been held in check, ebbing and flowing a bit plus or minus 10% of their baseline size. The net result is slightly more than a 30% reduction in the sum of the longest diameters of the target lesions, or in technical terms, a partial response as of the most recent restaging. In addition, her levels of CA19-9, which is a blood-based biomarker of pancreatic tumor burden and prognosis, have dropped from 30,000 to well below 5,000. The patient has also gained a substantial amount of weight on study, which is really great to see because pancreatic cancer patients usually deal with substantial weight loss from cachexia.
She has been doing well and has few adverse events and has experienced an improvement in quality of life, including an increase from 96 to 141 in the FAACT score, which is the functional assessment of anorexia cachexia therapy, which I've seen firsthand. For example, when the patient initiated the study, she required significant help from family due to pain and weakness. Now she can drive herself independently and has gained back a sense of self-reliance that she desired. Rarely do I see patients have liver lesions completely eliminated and gain weight with so few side effects. When I met her, she was cachectic and weak. Now she looks and feels healthier as a result of her improved appetite and weight gain. It is clear to me that atebumetanib is providing unique benefit to the patient that she would be unlikely to see with chemotherapy alone.
My colleagues and I have treated several patients in various arms of the atebumetanib trial, and we are excited that the Phase 3 study will begin dosing patients with this combination by mid-year. Atebumetanib has potential to improve long-term outcomes and quality of life for patients with pancreatic cancer. With that, let me hand the call back to Ben.
Thank you, Dr. Pelster. We are thrilled to hear how well this patient is doing on the trial. Please turn to Slide 14. Now, let's turn to an overview of our planned pivotal Phase 3 clinical trial, MapKeeper 301. This will be a global randomized trial in metastatic first-line pancreatic cancer. The study will enroll approximately 510 patients randomized to atebumetanib plus modified gemcitabine nab-paclitaxel versus standard gemcitabine nab-paclitaxel alone. Overall survival will be the primary endpoint. We aligned with both the FDA and EMA on the trial design in the fourth quarter of 2025, and we anticipate dosing our first patient in the middle of the year with top-line results anticipated in mid-2028. Please turn to Slide 15. In closing, we believe these data represent an extraordinary advantage in pancreatic cancer, a notoriously difficult-to-treat cancer.
Achieving 64% overall survival at 12 months, nearly double the historical benchmark, with excellent tolerability and meaningful improvements in quality of life, is something rarely seen in this disease. Our goal is not simply to shrink tumors, but to do so durably, safely, and in a way that allows patients to live much longer and have much better quality of life. In other words, quality and quantity. We have multiple near-term upcoming milestones, including sharing circulating tumor DNA analyses and updated survival from more than 50 patients, dosing the first patient in our Phase 3 trial, and the start of our Phase 2 combination studies in non-small cell lung cancer. Importantly, our cash runway extends into 2029, funding us through the pivotal data readout and through the initiation of additional trials in new combinations in cancers where we expect atebumetanib to perform well.
The results we have shown to date are extraordinary, and we strongly believe atebumetanib represents a unique late-stage opportunity in pancreatic cancer and beyond. And with that, we're happy to take questions, Operator.
Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. And again, we ask to give ample time to address everyone's questions. Please limit yourself to one question and one follow-up. We'll take our first question from Ally Bratzel at Piper Sandler.
Hey, good afternoon, team, and a big congrats from me on this data. Maybe a question on the Phase 3 design. Now that you finalized that with FDA, could you just kind of help us understand assumptions on median OS for the control arm? Is the eight and a half months we've seen for standard of care a good assumption? Or just any color there would be helpful. And then as a follow-up question, I think we all recognize how important safety and tolerability is to patients, and this is just such a big differentiator for atebumetanib. So it does look like you're including QOL measures as a secondary endpoint in the Phase 3. Can you just kind of talk some more to that, what PROs will you use, and then how that can affect positioning of when it comes to market? Thanks.
Yeah, thanks, Allyson. Appreciate the questions, and yeah, we couldn't be more excited for the Phase 3 study, MapKeeper 301. I think with OS as the primary endpoint, I think we're thrilled to be able to go with 64% overall survival that we've seen and reported today at 12 months. Just really sets us up very nicely going into this study, and we're excited to dose the first patient mid-year, so you're absolutely right. We are going to include quality of life metrics as part of the study, and I think that's so important because, as you heard from Dr. Pelster, we really are seeing just remarkable improvements in quality of life in these patients. I mean, to be able to drive again, just that kind of independence, regaining independence, is really remarkable.
It was important to us to have those quality of life metrics as part of the trial. And certainly, we believe the trial is extremely well-powered to detect really just the dramatic differences that we're seeing between the survival that you would expect from standard of care gemcitabine nab-paclitaxel and really what we're seeing with atebumetanib. I mean, to nearly double the overall survival at 12 months is just remarkable. We're really excited for the trial.
Thank you.
Thank you.
We'll move next to Ami Fadia at Needham.
Hi, good afternoon. Thanks for the data update today. I had two questions. Firstly, can you talk about, particularly in PDAC, how much can one rely on median PFS to predict median OS? And if you could sort of tie that up with the mechanism for atebumetanib and how that could translate into durability as we see that data mature. And maybe just sort of put in context for us, how important is quality of life in terms of maybe treatment choices for this patient population? Thank you.
Hey, Amy, thanks for the question. Well, look, overall survival is the gold standard, right? I mean, this is our sole primary endpoint. This is what matters most to patients, is how long they live. And that's why we're thrilled to have 64% overall survival at 12 months, nearly double the benchmark for standard of care, which is 35%. But that being said, progression-free survival is a surrogate endpoint, right? It's something that is helpful to kind of assess the robustness of the overall survival result that you're seeing. And that's why we're thrilled to see such a strong separation between our median overall survival at eight and a half months and the benchmarks from standard of care. Five and a half months is the benchmark for GNP.
So that full three months separation in terms of median PFS, we think, just adds further robustness to the strong overall survival results that we're seeing. So we're thrilled to see that kind of separation on progression-free survival. And I think ultimately, it speaks to the durability that we've built into this treatment, right? The deep cyclic inhibitors are designed to not drive resistance in quite the same way. And just to be clear, the median PFS is eight and a half months. I may have misspoken a minute ago, but the median progression-free survival we're seeing is eight and a half months versus five and a half for the standard of care benchmark. So just a really remarkable gap there, which, again, I think lends robustness to the overall survival advantage that we're seeing so clearly with 64% OS at 12 months.
Now, you asked about how important quality of life is, and I think it's incredibly important. Again, I think Dr. Pelster's case study really brings that home, right? I mean, this matters to patients, right? Patients don't just want more time. They want time that they can enjoy, right? To be able to drive independently, to be able to have an appetite and gain weight, not have to deal with harsh side effects to the same extent as other treatments. This is really, we mean it when we say it, quality and quantity, right? I think too often, with harsh cancer treatments, patients are forced to make this trade-off to essentially accept debilitating toxicity, whether it's nausea, vomiting, diarrhea, rashes, just terrible sacrifices on quality of life to gain quantity, to gain survival. And it doesn't have to be that way. It doesn't have to be that way.
We believe it's possible to have great quality of life and great overall survival. And I think the data we're showing today and the kinds of reports you're hearing from Dr. Pelster today and that you heard from Dr. Ocean and Dr. Botta on our call in November all show that it's possible, with atebumetanib, with deep cyclic inhibitors, for patients to have great quality of life and to have great quantity, great overall survival. And we're thrilled to be able to present that new option for patients, and we think it's going to be remarkable. So thank you for the question, Amy.
We'll take our next question from Jay Olson at Oppenheimer.
Oh, hey, thank you for providing this update and congrats on all the progress you're making on behalf of patients. We're curious about how Dr. Pelster would compare the profile of atebumetanib versus other emerging therapies for PDAC, especially based on atebumetanib's impressive OS results so far, along with its clean safety and tolerability profile. We're wondering, what would Dr. Pelster consider to be the ideal patient population for atebumetanib?
Oh, hey, Jay, thanks for the question. So we did let Dr. Pelster get back to treating her patients, but I think you heard from her, really her excitement about the pivotal study, the Phase 3 study. And I think it's easy to see why, given just the incredible dramatic improvement in quality of life that she's seeing in the patient that she described. And look, we've been so focused on the quality of life, but that patient's tumors are shrinking too. I mean, to have two liver mets rendered completely undetectable, I mean, liver mets are supposed to be the challenging ones in pancreatic cancer and not for atebumetanib. We just cut those two down to being rendered undetectable, which you heard Dr. Pelster say is really not something she commonly sees. So I think that's great to see. I think you heard it from Dr. Ocean and Dr.
Bharat on the call in November, right? To have a complete response, as Dr. Ocean described on the call in November, with a patient who's never felt better, to quote Dr. Ocean. And by the way, we have an update in the appendix of our slide deck that complete response, which was unconfirmed at the time of the call in November, has now confirmed. You can see that update on Slide 24. So confirmed complete response on that patient. So just this remarkable combination of shrinking tumors, but doing it differently, doing it in a way with durability, with quality of life. You heard it from Dr. Botta as well with his patient that was able to get this surgical resection, the Whipple procedure. And I think that's, and again, but to feel to have great quality of life together with that. So it's this combination of quality and quantity, right?
Great quality of life, great survival. And we think this is why there's just so much excitement for the Phase 3. You heard it from Dr. Pelster. You saw it in the quote in our press release in December from Dr. O'Reilly. It's Memorial Sloan Kettering excited for the Phase 3. You heard it from both Dr. Ocean and Dr. Botta. Everyone's excited for this Phase 3 because they're seeing the benefits. They're seeing the tumors shrink. They're seeing the overall survival, and they're seeing the quality of life. And it's really just a remarkable combination. We believe atebumetanib is going to be fantastic for these patients.
Okay, great. Thank you, Ben. That's super helpful, and congrats again on the results.
Thank you, Jay.
We'll go next to Graig Suvannavejh at Mizuho.
Hey, thank you very much for taking my questions. Happy New Year. A couple of questions for me. One, I was curious. I know overall survival is your primary endpoint. It's the gold standard. You did share some median PFS data in this 12-month update. I was wondering if you could maybe comment on what you might think the PFS rate might look like and what are the gating factors to be able to share that readout or that number. Secondly, just maybe a clarification for me. You've got a data update in the first half on your expanded enrollment of additional patients. I think you mentioned the update would include data from about 50 patients. Maybe just to clarify, is that an extra 16 on top of the 34, or is that an incremental 50 on top of the original 34?
Just on that, what should we be thinking in terms of the treatment follow-up period when you share that data set from those 50? Thanks.
Hey, Greg, thanks for the question and happy New Year. So with regard to progression-free survival, yes. So we're sharing today the median progression-free survival, eight and a half months median progression-free survival, which is just a remarkable advantage or improvement over the benchmark from the standard of care gem-nab, which is only five and a half months. So we're thrilled to see that really substantial increase in progression-free survival. And again, that's a surrogate endpoint. That's a predictor, albeit an imperfect one, of overall survival. But ultimately, overall survival is the gold standard. It's the primary endpoint. And we're thrilled to see that we're nearly doubling the overall survival at 12 months with 64% versus 35% for the standard of care benchmark. And by the way, our median follow-up time here is 13.4 months. 13.4 months.
While we're focused on 12 months because that's kind of the landmark that a lot of people look at, I mean, it stays at 64% out to that 13.4-month median follow-up, whereas the standard of care continues to decline. So at 13.4 months, standard of care is only about 31%. So actually, more than double the OS of standard of care at that 13.4-month mark. So we're thrilled about that. In terms of your second question, the data that we plan to share in the first half from this expanded cohort, right? It's more than 50 patients. So that includes both the 34 patients we're talking about today plus an additional 20 or so patients. So that's the expanded cohort. It's both. It's bringing in those additional patients. And if you'll recall, I mean, we talked about this in June, but we originally intended to enroll 30, enrolled 34.
And just the demand to get more patients onto this study was so strong that after a period of time, we essentially reopened it and took another 20 or so patients. And to your point, those patients have a shorter median follow-up time because they started much later, but it's approaching the point where together with the 34, I think that group of 50 is approaching the point that we're ready to talk about really in the first half. And I think, frankly, it's big news we're sharing today that the OS in that expanded cohort is trending consistently with the OS in the original 34 patients.
For everyone who's been kind of focused specifically on the specific 34 patients that we had here, the fact that adding another 20 patients in and you still see consistent overall survival, I think just adds yet another layer of robustness to the already really robust and remarkable results we're seeing with 64% OS at 12 months. Look, we hope to share those data at an upcoming medical meeting and with dosing the first patient in the Phase 3 mid-year, as we expect to do. I think the timing will be really good for that.
We'll go next to Andrew Berens at Leerink Partners.
Hi. This is Emily on for Andy. I guess I was wondering if you could provide any color on what portion of patients were treated in the second line and third line after the atebumetanib combo. And for those patients that did receive subsequent therapy, what treatments did they get? Thank you.
Yeah. Hey, Emily. That's a great question. So we know that about half the patients from our study went on to receive treatment in the second line setting that we have information about. And of those patients, the vast, vast majority received additional chemotherapy. So there's only one patient that we're aware of out of the entire 34 who went on to an experimental targeted agent. So I'm glad you asked because it's important to understand that this is not a group of patients that's going on in large numbers to experimental therapy. Again, there's only one of the 34 that we're aware of.
I think the fact that they're only receiving, really, if anything, mostly chemotherapy after treatment just lends further robustness to the strength of the overall survival result that we're seeing and the fact that atebumetanib really appears to be helping these patients stay alive much longer. I mean, to have essentially nearly a two-thirds chance of being alive at 12 months versus only about a third probability of being alive at 12 months with the standard of care Gem-Nab is just a really dramatic change for patients. To be able to do that with great quality of life, I mean, we're just so excited for atebumetanib. We think it compares so favorably to anything else that's out there in development in the competitive landscape. We believe we'll be best in class, and we have the prospect to become standard of care with the modified gemcitabine and paclitaxel.
That concludes our Q&A session. I will now turn the conference back over to Ben Zeskind for closing remarks.
Great. Well, I want to thank everyone for joining our call today. We'd particularly like to thank all the patients and the investigators involved in our ongoing studies, and we look forward to updating you on further progress in the coming year. Thank you, everyone. Have a good night.
This concludes today's conference call. Thank you for your participation. You may now disconnect.